Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase.
The Saccharomyces cerevisiae Mec1-Ddc2 protein kinase (human ATR-ATRIP) initiates a signal transduction pathway in response to DNA damage and replication stress to mediate cell cycle arrest. The yeast DNA damage checkpoint clamp Ddc1-Mec3-Rad17 (human Rad9-Hus1-Rad1: 9-1-1) is loaded around effector DNA and thereby activates Mec1 kinase. Dpb11 (Schizosaccharomyces pombe Cut5/Rad4 ... or human TopBP1) is an essential protein required for the initiation of DNA replication and has a role in checkpoint activation. In this study, we demonstrate that Dpb11 directly activates the Mec1 kinase in phosphorylating the downstream effector kinase Rad53 (human Chk1/2) and DNA bound RPA. However, DNA was not required for Dpb11 to function as an activator. Dpb11 and yeast 9-1-1 independently activate Mec1, but substantial synergism in activation was observed when both activators were present. Our studies suggest that Dpb11 and 9-1-1 may partially compensate for each other during yeast checkpoint function.
Mesh Terms:
Cell Cycle, Cell Cycle Proteins, DNA Damage, DNA Replication, DNA-Binding Proteins, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Schizosaccharomyces
Cell Cycle, Cell Cycle Proteins, DNA Damage, DNA Replication, DNA-Binding Proteins, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Schizosaccharomyces
J. Biol. Chem.
Date: Dec. 19, 2008
PubMed ID: 18922789
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